The major challenge facing Pfs25-based TBV development is to find a formulation with great safety profile and capable of inducing sustained high antibody responses. We have demonstrated that conjugating Pfs25 with carrier proteins OMPC of Neisseria meningitides, ExoProtein A (EPA) of Psuedomonas aeruginosa, or Pfs25 self, greatly enhance the immunogenicity of the recombinant Pfs25 produced in Pichia pastoris. We have produced recombinant EPA (rEPA), and developed a process to conjugate Pfs25 with rEPA. Various conjugation chemistries and methods were evaluated for optimal immunogenicity and a robust conjugation processes. The biochemical properties of Pfs25-EPA were characterized and the conjugates were evaluated in animals for their immunogenicities. The immune sera induced by the conjugate vaccine blocked parasite development in mosquitoes. A process was developed to produce a pilot scale cGMP lot conjugate. Animal studies were conducted to evaluate enhancement of immunogenicity by novel adjuvants. A Phase 1 trial has been planned to test safety, immunogenicity, and ex-vivo transmission blocking activity in humans.